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Predictive values of serum insulin kinetics for reversion of impaired glucose tolerance to normal glucose tolerance and the effects of voglibose treatment: a retrospective post hoc analysis of a Japanese phase III study


In a phase III study, voglibose was shown to reduce the risk of development of type 2 diabetes mellitus (T2DM) by 40.5 % in Japanese individuals with impaired glucose tolerance (IGT), and appeared to promote reversion of IGT to normal glucose tolerance (NGT). In a retrospective, post hoc analysis, data from this study, plus follow-up findings from subjects who achieved NGT during the study and who were off-treatment, were analyzed to investigate serum insulin kinetic parameters which might be predictors of IGT reversion to NGT, and maintenance of NGT once achieved. The effects of voglibose on serum insulin kinetics in individuals with IGT were also assessed. Subjects with IGT (n = 1778) were randomized to receive voglibose (0.6 mg/day) or placebo for a mean of 48.1 weeks. During treatment, 1053 subjects achieved NGT, 569 continued to have IGT, and 156 developed T2DM. Analysis of baseline characteristics in each outcome group showed that subjects with higher 30-min serum immunoreactive insulin (IRI) levels in a 75 g oral glucose tolerance test (OGTT) or higher insulinogenic indexes at baseline were more likely to achieve NGT, whether they received voglibose or placebo. Among subjects who achieved NGT, the mean increase in OGTT 30-min IRI level from baseline to endpoint was significantly greater after treatment with voglibose than with placebo. Individuals who had higher OGTT 30-min IRI levels when achieving NGT seemed more likely to sustain this state. Thus, insulin secretion kinetics appeared to predict reversion of IGT to NGT and maintenance of NGT once achieved.

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  1. Each HbA1c value (%) is reported as HbA1c (JDS) [%]. HbA1c (National Glycohemoglobin Standardization Program) (%) = 1.02 × HbA1c (JDS) (%) + 0.25 % [9].

  2. Insulinogenic index (I.I.) = [IRI (30 min) − IRI (0 min)]/[plasma glucose (30 min) − plasma glucose (0 min)].


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This study was funded by an unrestricted research grant from Takeda. We thank the sponsor for assistance with data monitoring and gathering, and for editorial support that was provided by Steve Clissold, Content Ed Net. We also acknowledge the investigators and other staff members who participated in this study. The study centers were as follows: Chonan Clinic, Ishikawa Clinic, Nakahashi Naika Clinic, Kadono Clinic, Aoki Clinic, Takahashi Clinic, MATSUDA Medical Clinic, Kitanodohri Naika Junkanki Clinic, Kurihara Diabetic Care Clinic, Sawai Clinic, Mita Medical-Cardiovascular Clinic, Toyooka Chuo Hospital, Gorinbashi Naika Hospital, Sapporo Century Hospital, Ashino Medical Clinic, Hyuga Clinic, Odori Koen Junkanki Clinic, Asahiyama Naika Clinic, Hokkaido University Hospital, Teine Keijinkai Hospital, Jusendo Clinic, Jizankai Medical Foundation Tsuboi Cancer Centre Hospital, Naka Memorial Clinic, Hitachi. Mito General Hospital, Toride Kyodo General Hospital, Tsukuba Souai Hospital, Moriya Keiyu Hospital, Tsukuba Memorial Hospital, Healthcare Corporations Association Kunwa-Kai Aiwa Clinic, Toho University Sakura Medical Center, Shimai Medical Clinic, Kanjinkai Medical Corporation Fussa Clinic, Ooimachi Medical Clinic, Medical Corporation Shiratorikai Shiratori Medical Clinic, Showa General Hospital, Kanto Medical Center NTT EC, Tokyo Clinical Research Organisation for Medicine Clinic, Kanda Clinic, Tsukiji Clinic, Toyomi Clinic, Shinagawa East One Medical Clinic, Shiodome Oak Clinic, Miho Clinic, Ohsaki Heart Clinic, Kita Aoyama D Clinic, Sasaki Hospital, Yokohama Shinmidori General Hospital, Kubo Clinic, Minami Medical Clinic, Kawasaki Saiwai Clinic, Medical Corporation Kojinkai Niigataminami Hospital, Sado General Hospital, Daisinkai Medical Corporation Ookuma Hospital, Yamane Hospital, MEDOC, Takada Naika Clinic, Sakura Clinic, Nishikyoto Hospital, Medical Corporation Syoyu-kai Ameno Clinic, Kajiyama Clinic, Medical Corporation Hayashi-Katagihara Clinic, Osaka Clinical Research Organisation for Medicine Clinic, Kishiwada Tokushukai Hospital, Izumi Municipal Hospital, Saiseikai Nakatsu Hospital OSAKA, Sakurabashi Watanabe Hospital, Usui Internal Medicine/Gastroenterology Department Clinic, Tatsumi Clinic, Ichida internal Clinic, Medical corporation Kondou Clinic, Kawashima Clinic of Medicine, Umeda Oak Clinic, Institute of Biomedical Research and Innovation, Ikeda Hospital, Kinki Central Hospital of Mutual Aid Association of Public School Teachers, Nara Prefectural Gojo Hospital, Hiraoka Medical Clinic, KKR Takamatsu Hospital, Ritsurin Hospital, NTT West Takamatsu Hospital, JA Yashima General Hospital, National Hospital Organization Kochi National Hospital, Hosogi Hospital, Koseinenkin Kochi Rehabilitation Hospital, Kochi Memorial Hospital, Kohryo Hospital, Susaki Kuroshio Hospital, Clinic Tenjin kita, Fukuoka University Hospital, St Mary’s Hospital, Fukuoka Tokushukai Medical Centre, Sada Hospital, Harasanshin Hospital, Jinnouchi Hospital, Tamana Central Hospital, Naika Abe Clinic, Koga General Hospital, Karimata Medical Clinic, Uranishi Clinic, Medical Corporation HSR Nakamura Clinic, Kariyushi Clinic, Urasoe Sogo Hospital, Tokuyama Clinic.

Conflict of interest

Regarding this article, R.K., N.T., Y.I., A.K., K.S. and K.K. have received consultancy fees from Takeda. No other potential conflicts of interest relevant to this article were reported. H.S. is an employee of Takeda Pharmaceutical Company Limited.

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Correspondence to Ryuzo Kawamori.

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Kawamori, R., Tajima, N., Iwamoto, Y. et al. Predictive values of serum insulin kinetics for reversion of impaired glucose tolerance to normal glucose tolerance and the effects of voglibose treatment: a retrospective post hoc analysis of a Japanese phase III study. Diabetol Int 3, 209–216 (2012).

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  • Voglibose
  • Impaired glucose tolerance
  • 75 g Oral glucose tolerance test
  • Serum immunoreactive insulin